Hydrochloric Acid → HCID 178495651, Verbindung

HRID 1751638Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751638
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]1[NH:20][C:19]2[C:21]3[C:26]([CH:27]=[CH:28][C:18]=2[N:17]=1)=[CH:25][C:24]1[C:29]2[C:34]([CH2:35][O:36][C:23]=1[CH:22]=3)=[CH:33][C:32]([C:37]1[CH:38]=[CH:39][C:40]3[N:44]=[C:43]([C@@H:45]4[CH2:49][CH2:48][CH2:47][N:46]4[C:50](=[O:60])[C@@H:51]([NH:55][C:56]([O:58][CH3:59])=[O:57])[CH:52]([CH3:54])[CH3:53])[NH:42][C:41]=3[CH:61]=1)=[CH:31][CH:30]=2)=O)(C)(C)C.Cl.[CH3:63][O:64][C:65]([NH:67][C@H:68]([C:72]1[CH:77]=CC=C[CH:73]=1)[C:69](O)=[O:70])=[O:66].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C.C(O)C>[CH3:59][O:58][C:56]([NH:55][C@@H:51]([CH:52]([CH3:53])[CH3:54])[C:50]([N:46]1[CH2:47][CH2:48][CH2:49][C@H:45]1[C:43]1[NH:42][C:41]2[CH:61]=[C:37]([C:32]3[CH:33]=[C:34]4[CH2:35][O:36][C:23]5[CH:22]=[C:21]6[C:26]([CH:27]=[CH:28][C:18]7[N:17]=[C:16]([C@@H:9]8[CH2:10][C@H:11]([CH2:13][O:14][CH3:15])[CH2:12][N:8]8[C@@:68]([NH:67][C:65](=[O:66])[O:64][CH3:63])([CH:72]([CH3:77])[CH3:73])[CH:69]=[O:70])[NH:20][C:19]=76)=[CH:25][C:24]=5[C:29]4=[CH:30][CH:31]=3)[CH:38]=[CH:39][C:40]=2[N:44]=1)=[O:60])=[O:57]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178495652HCID 178495652, Verbindung

Produkt 1

HCID 178495651HCID 178495651, VerbindungAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of (2S,4S)-tert-butyl-2-(9-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (156 mg, 0.18 mmol), ethanol (3 mL) and concentrated HCl (1 mL) was heated to 60° C. for 1 hour. The reaction was concentrated and the crude material dissolved in DCM (6 mL). This solution was concentrated and to (68 mg, 0.09 mmol) of this material was added a solution of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (21 mg, 0.12 mmol) and COMU (41 mg, 01 mmol) in DMF (1 mL). To the resulting solution was added diisopropylethylamine (50 μL, 0.28 mmol). After stirring for 2 hours at room temperature, the reaction was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 44% ACN/H2O+0.1% TFA). The product fractions were lyophilized to give methyl {(2S)-2-[(2S,4S)-2-{9-[2-((2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl}-4-(methoxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (32 mg, 40%). MS (ESI) m/z 886 [M+H]f.

Aufarbeitung

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DCM (6 mL)
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by preparative reverse phase HPLC (Gemini, 15 to 44% ACN/H2O+0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-0a0b92f2413e4c2792fcaa259d8a0434
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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